CRISPR-Cas9 editing of agricultural crops and medicinal plants: toward a cornucopia of natural products

Chapter 6 - Genome editing: applications for medicinal and aromatic plants

Medicinal and aromatic plants are offered in a wide variety of products on the market. At least every fourth flowering plant is used. The enormous demand in botanicals results in a huge trade from local to international level. In the 1990s, the reported annual world-wide importation of pharmaceutical plants amounted on average to 400,000 t valued at USD 1,224 million. The international trade is dominated by only few countries. About 80 % of the world-wide imports and exports are allotted to only 12 countries with the dominance of temperate Asian and European countries. Whereas Japan and the Republic of Korea are the main consumers of pharmaceutical plants, and China and India are the world’s leading producing nations, Hong Kong, the USA and Germany stand out as important trade centres. Until now, the production of botanicals relies to a large degree on wildcollection. However, utilization and commerce of wild plant resources are not detrimental in themselves, but, for example, the increasing commercial collection, largely unmonitored trade, and habitat loss lead to an incomparably growing pressure on plant populations in the wild. World-wide an estimated 9,000 medicinal plant species are threatened. Conservation concepts and measures which have to meet future supply and the provisions of species conservation range from resource management, cultivation, shifting processing from consumer to source countries, species conservation to trade restrictions or even trade bans. Medicinal and aromatic plants are of high priority for conservation action, as wild-crafting will certainly continue to play a significant role in their future trade: the sustainable commercial use of their biological resources may provide a financial instrument for nature conservation. INTRODUCTION Phytopharmaceuticals, also some pharmaceuticals, herbal remedies, dietary supplements, homeopathics, medicinal and herbal teas, liqueurs, spirits, sweets, aromas and essences, perfumes, cosmetics, colouring agents, varnishes, fireworks, and detergents – plant-based products offered in a wide variety on the market. Whereas in some goods the herbal ingredients are evident, e.g. in teas or in herbal remedies where they are declared on the packaging, in other products the botanically source is more secret: the bitter taste of Campari is based on the Common Centaury (Centaurium erythraea), and the fenugreek (Trigonella foenum-graecum) contains steroid-saponins which are extracted for use in oral contraceptives. The use of botanical raw material is in many cases much cheaper than to use chemical alternative substances. As a consequence, there is an enormous demand in botanicals resulting in a huge trade, on local, regional, national and international level for domestic use and for commercial trade. Different aspects are associated with the trade in medicinal and aromatic plant material, the trade structure, trade volumes and values, the herbs used and their production, the ecological and socio-economic impacts of the trade, and the management of the botanical resources. Proc. XXVI IHC – Future for Medicinal and Aromatic Plants Eds. L.E. Craker et al. Acta Hort. 629, ISHS 2004 Publication supported by Can. Int. Dev. Agency (CIDA) 178 MEDICINAL AND AROMATIC PLANTS IN USE Species in Use World-wide, it is estimated that up to 70,000 species are used in folk medicine (Farnsworth and Soejarto, 1991). The WHO reports over 21,000 plant taxa used for medicinal purposes (Groombridge, 1992). Unfortunately, there is no idea how many species are used in the other areas of use, like cosmetics, spirits or aromas which makes determining exactly the number of all medicinal and aromatic plant species used worldwide impossible. However, it can be stated, that at least every fourth plant is in use, a calculation based upon the estimated total number of 300-350,000 flowering plants. The number of medicinal and aromatic plant species used in some regions are impressive: In India, which is said to have probably the oldest, richest and most diverse cultural traditions in the use of medicinal plants, about 7,500 species are used in ethnomedicines (Shankar and Majumdar, 1997) which is half of the country’s 17,000 Indian native plant species. In China, the total number of medicinal plants used in different parts of the country add up to some 6,000 species according to Xiao (1991) and to over ten thousand according to He and Sheng (1997). Of these, approximately 1,000 plant species are commonly used in Chinese medicine, and about half of these are considered as the main medicinal plants (He and Sheng, 1997). In Africa, over 5,000 plant species are known to be used for medicinal purposes (Iwu, 1993). In Europe with its long tradition in the use of botanicals, about 2,000 medicinal and aromatic plant species are used on a commercial basis (Lange, 1998). In Germany, Lange (1996) identified not less than 1,500 taxa as sources of medicinal and aromatic plant material. In Spain, it is estimated that 800 medicinal and aromatic plant species are used of which 450 species are associated with commercial use (Blanco and Breaux, 1997; Lange, 1998). Geographical Origin of the Species in Use Herbs used in a country can be either indigenous or native to other regions or even continents. The share of both plant groups depends on the country’s cultural preferences, importance of traditional medicines, history, trade relations, and of course of the wealth or poverty of a country. Traditional medicines are playing an important role in many parts of the world. In south and southeast Asia, the Ayurveda, Unani and Siddha medicines are widely distributed and based on not less than 400, 500 respective 1,800 native Indian plant species (Shankar and Majumdar, 1997). The TCM, the traditional medicine of eastern Asia, relies in most cases on indigenous plant species. Traditional healers in many African countries rely on local or at most regional plant material (Marshall, 1998). In Bulgaria, about 750 native plant species, or 20 % of the total flora, are used in folk medicine. Of these, 200300 species are most commonly used (Hardalova, 1997). Further, in Albania, 205 native plant species are used as sources of botanicals (Vaso, 1997; Lange, 1998). In Hungary, some 270 native medicinal and aromatic plant taxa are used, 180-200 of which are officially recognised by the Hungarian Pharmacopoeia (Bernath, 1996). Ozhatay et al. (1997) list a total of 337 native taxa that have been commercially traded in Turkey since at least 1990 (Lange, 2001). From the French pharmacopoeia and lists of medicines Goi et al. (1997; Lange, 1998) noted some 900 taxa, of which almost half are native to Europe. This means, that many countries rely on a major part on their own plant diversity. Many of them cannot afford to import foreign botanicals, finished herbal products or even phytopharmaceuticals and the country’s own “biodiversity” is mainly offered in a crude form or at most as little processed products on the market. On the other side, there are the developed countries which use besides indigenous plant species a lot of non-native species and process them in their well developed pharmaceutical, cosmetic and extract-producing industry. Accordingly, the plant material is offered to the consumers as mainly packed and finished products, and the crude material plays a minor role in the retail trade. This features apply above all to the highly

Biosynthesis, purification, characterization and uses of natural compounds in plants Natural products impart immense chemical diversity to the plant kingdom, owing to more than 200,000 specialized metabolites (SM), many of which are derived from phenylpropanoid, terpenoid and alkaloid biosynthetic pathways (Sousa Silva et al., 2019) . Furthermore, these molecules are distinguished on the basis of their modifications such as glycosylation, acylation, and prenylation (Wu and Lei, 2022) . Aromatic and medicinal plants serve as abundant sources of natural products, many of which possess significant benefits for human health. These benefits include as the prevention and/or treatment of various cancers, as well as inflammatory, cardiovascular and neurodegenerative diseases (Che and Zhang, 2019). Additionally, these SM exhibit antimicrobial, antiviral and antidiabetic properties (Mohammed and Khan, 2022). Apart from species and/or organ specific accumulation patterns, natural products occur in response to various abiotic and biotic stresses. They serve diverse biological functions, acting as attractants, repellants and other olfactory signaling molecules involved in olfactory communication. Additionally, they play an essential role in growth and development (Weng et al., 2021) . In certain cases, these natural products are localized within specific tissues and/or specialized cells such as leaf epidermal trichomes (Liu et al., 2019) . To harness the potential of plant natural products for human health and the agrifood industries it is crucial to gain in-depth understanding of their biosynthetic pathways and bioactivities. However, due to limited knowledge regarding the genetic factors influencing natural product production in plants, strategies for feasible extraction and purification from plants are required. This task presents a considerable challenge due to typically low abundance of SM in plants. Dendrobium officinale, a traditional medicinal herb and a new functional food (Chen et al., 2021), still holds many mysteries regarding its phytochemical composition, particularly its bioactive alkaloids The limited knowledge can be attributed, in part, to the absence of robust analytical techniques. In their work, Song et al. developed an Frontiers in Plant Science frontiersin.org 01

Renewed interest in medicinal and aromatic plants during the past 20 years has brought surging markets and production opportunities for these plant species. To enhance and maintain market growth, however, MAP production systems, whether cultivated or collected, will need to ensure sustainable production of quality plant materials that have been wholesomely grown and processed. The growing familiarity of western consumers with medicinal and aromatic plants places a premium on standardized plant materials that are organically produced and meet expectations for efficacy. Currently, market demand for MAP is nurtured by consumer demographics and by favorable impressions of bioactivity, but this demand remains susceptible to myths, traditions, and science reports associated with the plant materials. By addressing the problems of standardization and verifiable marker compounds along with issues such as plant domestication, conservation, biotechnology, and others that affect plant cultivation, producers and processors can assure acceptable products reach the marketplace and crop production opportunities will continue to grow. Introduction A recent resurgence of interest in medicinal plants in many Western nations, the continued dependence of people in much of the world on these species, and the advent of a globalized economy has brought sustainability challenges to the medicinal plant trade. The modern market for medicinal plants has, in general, grown over the past 15 years (Fig. 1), but remains fragile, subject to governmental regulations, research findings, and media publicity along with the usual factors associated with supply and demand. Indeed, many challenges to the continued growth of the market exist, including appropriate education of consumers, assurances of high quality products, and availability of a sustainable supply of plant material. The development of patentable, synthetic pharmaceuticals in the 1930s and 1940s in America and other Western countries (Table 1) resulted in the active abandonment of medicinal plants in health care, leaving new generations of both health care practitioners and the general populace with only a limited history, culture, and understanding about the appropriate use of medicinal species for preventing and treating human ailments (Craker and Gardner, 2003). Consumer confidence in pharmaceutical drug development, enhanced by the discovery of antibiotics and vaccinations that prevent or treat many diseases has lately decreased as drug costs escalate and major health problems, such as cancer, AIDS, cardiovascular disease, and numerous other problems continue to exist. An array of interests from medical professionals essentially committed to “modern” pharmaceuticals, consumers seeking alternative health care options, and herbalists promoting the use of medicinal and aromatic plants can convert challenges to market opportunities if growers and processors provide safe, useful plant products and educate consumers and health care professionals on benefits of medicinal plant products. Education of consumers and healthcare practitioners about the correct use of medicinal and aromatic plants and plant extracts will help ensure the continued recognition of the value of these products. For example, Western consumers accustomed Proc. WOCMAP III, Vol 2: Conservation Cultivation & Sustainable Use of MAPs Eds.: A. Jatisatienr, T. Paratasilpin, S. Elliott, V. Anusarnsunthorn, D. Wedge, L.E. Craker and Z.E. Gardner Acta Hort. 676, ISHS 2005 26 to taking a pharmaceutical drug and experiencing the effect of the drug within minutes to hours must learn that an herbal product that may take much longer to exhibit noticeable activity. Similarly, consumers and producers must replace the concept of taking drugs to treat pre-existing conditions with the concept of taking medicinal plants to improve general health and to treat both clinical and sub-clinical conditions. If consumers and health care providers are unfamiliar with the concepts of medicinal herb use, they cannot be expected to seek, recommend, or use these plants as medicine. Consumer Demographics As with any commodity, sales and use of medicinal plant products are influenced by the type of people that use these products. Indeed, a good share of the growth in sales of medicinal and aromatic plants and other natural products over the past 15 years can be attributed to the growth of certain demographic groups. Immigrants from Asia and Latin America have popularized a new palette of herbs and spices in restaurants and homes in the United States. This popularization has been such that U.S. spice consumption grew from 2 pounds per capita in 1976 to 3.2 pounds per capita in 1995 (Anonymous, 1998) (Fig. 2). Contributing to the increase in spice consumption is a change in lifestyle in many industrialized nations. The movement of women, historically the people responsible for meal preparation, from the home to workplace has altered traditional roles, requiring easier food preparation within the limited time available after work. In these instances, spices are frequently used to enhance the flavor of homemade and prepared meals. A highly significant trend among consumers is the increase in consumers interested in environmental issues, the so-called “green” consumers (Roper, 2002). Such consumers are willing to pay a premium for eco-friendly products, including organic foods, recycled products, and herbal remedies. These consumers value natural alternatives to conventional products including foods and medicines, thus medicinal plant products and natural food flavorings are favored by these consumers. Media Influences Media stories featuring medicinal plants appear highly influential in consumer demand and acceptance of medicinal plants. While medicinal plants were featured positively in several highly publicized stories in the late 1990s (Greenwald, 1998; Johnson et al., 1997), many of the more recent stories have been negative with concerns focused on several plant species (such as kava and ephedra) (Burros, 2002; Strugatch, 2002), with few headlines highlighting the benefits or proper use of medicinal plants. Most of the negative stories are concerned with the lack of standardization of dose or with reports of results from poorly designed research studies (Brody, 1999). Product Quality The popularization of medicinal plants in Western nations during the 1990s encouraged the formation of numerous new companies producing herbal medicines. Unfortunately, the quality of the plant materials (including differences due to natural variation, cultivation practices, and post harvest handling) and processing vary among companies, and thus the quality of oils and other extracts is highly variable. Surveys by independent laboratories have demonstrated significant variation in the quality and reported content of packaged herbal remedies (Anonymous, 2001; ConsumerLab, 2002). News reporting of such variation undoubtedly lowers consumer and health care provider confidence in medicinal plant products. Standardization of herbal products is the most commonly suggested solution for overcoming the natural variation of constituents in plant material. While standardization can help ensure product quality, recognized drawbacks to standardization exist. For example, in many plant species the active constituents of the species are not fully known. Secondly, a combination of plant constituents may be responsible for biological action of the plant or plant extract. Yet, if standard guidelines for marker compounds can be recognized and if plant selection, cultivation methodology, and processing can be

Plants are the richest source of specialized metabolites. The specialized metabolites offer a variety of physiological benefits and many adaptive evolutionary advantages and frequently linked to plant defense mechanisms. Medicinal plants are a vital source of nutrition and active pharmaceutical agents. The production of valuable specialized metabolites and bioactive compounds has increased with the improvement of transgenic techniques like gene silencing and gene overexpression. These techniques are beneficial for decreasing production costs and increasing nutritional value. Utilizing biotechnological applications to enhance specialized metabolites in medicinal plants needs characterization and identification of genes within an elucidated pathway. The breakthrough and advancement of CRISPR/Cas-based gene editing in improving the production of specific metabolites in medicinal plants have gained significant importance in contemporary times. This article imparts a comprehensive recapitulation of the latest advancements made in the implementation of CRISPR-gene editing techniques for the purpose of augmenting specific metabolites in medicinal plants. We also provide further insights and perspectives for improving metabolic engineering scenarios in medicinal plants.

Chapter 9 - CRISPR/Cas9-mediated genome editing in medicinal and aromatic plants: developments and applications

Medicinal plants produce important pharmaceuticals, but these compounds are often present at low levels or only in specific tissues; in addition, many medicinal plants produce small amounts of biomass and are difficult to cultivate. Genome editing for agronomic traits and metabolic engineering holds promise for improving pharmaceutical production, and genome-editing applications in medicinal plants have expanded as genome-editing techniques have advanced. For example, genome editing has been used to regulate the production of phenolic acids and tanshinone metabolites of Salvia miltiorrhiza in medicinal plants. In this review, we synthesize the current knowledge on the development and applications of gene-editing tools in medicinal plants. Furthermore, we summarize the limitations of genome editing in these species and propose solutions for addressing these challenges to fully harness this technology for improving these important plants. We focus on novel technologies to enhance the regeneration rates of transgenic plants, artificial intelligence-assisted multiomics approaches for predicting editing efficiency, key components that optimize genome-editing efficacy, and the development of innovative gene-editing systems. Finally, we offer perspectives on advancing metabolic engineering strategies for medicinal plants.

In the present book, to give more experimental data using the phytochemical techniques and medicinal plants, research papers, lead articles and review papers contributed by several researchers are included. This book contains 35 s from various experts covering medicinal plants and the experimental data using the methods of identification using physical characteristics and spectroscopy which includes UV, IR, NIR, Mass and NMR. In various s, antioxidant potentials of mushrooms, seaweeds and medicinal plants, isolation of compounds from plants and their biological activities, novel near infra red application in natural products, in silico studies of anti-inflammatory compounds, molecular docking of natural products, CNS depressant activity of medicinal plants, isolation of antifungal proteins from medicinal plants, plant tissue culture, in vitro cell line selection for enhanced production of secondary metabolites, isolation of compounds from cell suspension cultures, X-ray crystal structure analysis of compounds from medicinal plants, synthesis and bioactivity of polycyclic spiroheterocyclic compounds are given in details. This book will prove useful to the students, scientists, researchers, professionals in the field of Plant Science, Pharmaceutical, Chemical Engineering, Biotechnology, Medicinal and Aromatic Plants, Forestry and Horticulture.

Effects of bio-fertilizers on the production of specialized metabolites in Salvia officinalis L. leaves: An analytical approach based on LC-ESI/LTQ-Orbitrap/MS and multivariate data analysis

Medicinal and aromatic plants (MAPS) represent a consistent part of the natural biodiversity endowment of many countries in Africa. The role and contributions of medicinal plants to healthcare, local economies, cultural integrity and ultimately the well-being of people, particularly the rural poor, have been increasingly acknowledged over the last decade. The demands of the majority of the populace for medicinal plants have been met by indiscriminate harvesting of spontaneous flora, including those in forests. This has resulted in severe loss of habitat and genetic diversity. The utilization of medicinal and aromatic plants (MAPs) as a source of fuel, building material, food, fodder, and fibre, in African countries has, however, led to a resurgence of natural product- based industries and pharmaceutical products. This had been spurred by the interests of the developed countries for traditional medicine and natural products. Furthermore, many African medicinal plants are well-known in the international markets, e.g. Ancistrocladus abbreivatus, a Cameroun plant with anti-HIV potential. Therefore, sustainable management and conservation of these endangered medicinal plant species are important not only because of their value as potential therapeutics, but also due to worldwide reliance on traditional medicinal plants for health. Effective conservation strategies for medicinal plant should take place within four main areas: in-situ andex-situ conservation, education and research. Saving Africa’s medicinal plant resources from extinction calls for intensive management and conservation, more research and increased level of public awareness about our vanishing heritage. Key words: African, health care delivery, medicine, harvesting.

Every year more than 400,000 tons of medicinal and aromatic plants from approximately 3,000 species are traded internationally, according to TRAFFIC, a nonprofit watchdog group that monitors commerce in natural products. (Up to 70,000 species are used medicinally worldwide, most of them locally.) Such a growth in demand for these plants threatens natural resources, since about 80% of commercially traded species are gathered from the wild, according to the World Conservation Union (IUCN). In February 2007, several groups concerned about potential adverse effects of this rise on plant habitats announced an international standard designed to preserve nature’s medicine chest for future generations. A year later, the standard appears to be bearing fruit. The IUCN Medicinal Plant Specialist Group, IUCN Canada, the German Federal Agency for Nature Conservation, WWF Germany, and TRAFFIC proposed the standard and coordinated several rounds of international vetting in 2005 and 2006. The new International Standard for Sustainable Wild Collection of Medicinal and Aromatic Plants (ISSC-MAP) is intended to balance the needs of people whose traditions and livelihood depend on these species with the plants’ long-term survival in their native habitats. The new standard is based on six principles related to maintaining wild resources, preventing negative environmental impacts, respecting customary rights (for example, of indigenous populations), and exercising responsible management and business practices. Plant scientists also drew on earlier guidelines both for the conservation of medicinal plants and for good agricultural and collection practices. “We did not want to reinvent the wheel,” says Susanne Honnef, TRAFFIC medicinal plant officer with WWF Germany, “so the standard builds on existing frameworks.” The new standard involves all actors along the supply chain—from wild plant harvesters to sellers—in a process for determining how to sustainably conduct harvests and trade, says Honnef. The standard also outlines practices for monitoring the impact of harvests over time. Honnef says the standard will protect important natural resources. As the benefits of sustainable use become more broadly recognized, harvesters will be encouraged to protect the ecosystems that support their livelihoods. And government agencies will have tools for defining benchmarks in a trade that is often informal and that falls through the cracks between groups that manage agriculture and forestry. The standard was tested in preliminary trials undertaken in six countries. Over 6 months in 2007, for example, 2 Indian communities used the standard to gauge population health of 6 commercially traded species, says Giridhar Kinhal, special projects coordinator for Foundation for Revitalisation of Local Health Traditions, a nonprofit scientific and research organization in Bangalore. Based on that trial, says Kinhal, the communities saw improved regeneration of the studied plant populations, but also reported the need for further guidance in assimilating these outcomes into resource management. Next comes a 2-year implementation phase at sites in Asia, Africa, southeast Europe, and South America. Danna Leaman, chair of the IUCN Medicinal Plant Specialist Group and a member of the advisory group that guided the development of ISSC-MAP, says, “A concrete activity like this is a real step forward” for the IUCN, which has worked for years to engage industry in biodiversity protection. Indeed, ISSC-MAP goes even further than current guidance such as Fair Trade and Organic certification. For example, it has been up to individual inspectors to determine whether a wild collection operation meets the requirements for Organic certification. Josef Brinckmann, vice president for research with manufacturer Traditional Medicinals, says that although the wild botanicals they use qualify for Organic certification, some sites will need further work to conform with all 6 principles of the ISSC-MAP. “Many of these certified Organic wild collection sites would need a few years to make the necessary changes for conformance with the ISSC-MAP standard,” he says. Yet, Brinckmann adds, the extra work will be worthwhile if compliance with the standard can help a company demonstrate unequivocably that its operations help maintain the botanical resource. Brinckmann points to Asia and Europe as places where the standard may first have a significant impact in alleviating intense harvest pressures. “China and India are the two largest producers and exporters of medicinal plants in the world,” he notes. Southeastern European countries and Russia are also important in the world market.

<div>Plants are continually subjected to a range of physical and biological</div><div>stressors throughout their growth period. Insects and pests, like other biotic stressors,</div><div>have created significant concerns about lower productivity, which jeopardizes</div><div>agricultural production. Genome engineering, also known as genome editing, has</div><div>emerged as a cutting-edge breeding technique capable of altering the genomes of</div><div>plants, animals, microbes, and humans. Since ancient times, humans have used</div><div>medicinal plants for food, medicine, and industrial purposes. Both traditional</div><div>biotechnology and more recent next-generation sequencing (NGS) methods have been</div><div>used successfully to improve natural chemicals derived from plants with medical</div><div>potential. To modify the genome at the transcriptional level, protein-based editing</div><div>approaches like zinc-finger nucleases (ZFNs) and transcription activator-like end</div><div>nucleases (TALENs) were previously frequently employed. CRISPR/associated9</div><div>(Cas9) endonucleases are a powerful, resilient, and precise site-directed mutagenesis</div><div>method in transcriptome gene editing. CRISPR/Cas9 genome editing employs specially</div><div>created guide RNAs to detect a three-base pair protospacer adjacent motif (PAM)</div><div>sequence situated downstream of the target DNA. The current review compiles current</div><div>research published between 2010 and 2020 on the use of CRISPR/Cas9 genome-editing</div><div>technologies in traditional medicines, describing significant innovations, difficulties,</div><div>and prospects, as well as noting the technique's broader application in crop and lesser</div><div>species. The CRISPR/Cas9 genome editing method has been utilised successfully in</div><div>plants to boost agricultural productivity and stress tolerance.</div><div>Despite this, only a small number of medicinal plants have been altered using the</div><div>CRISPR/Cas9 genome editing technique because to a lack of appropriate</div><div>transformation and regeneration techniques, and also a lack of comprehensive genome</div><div>and mRNA sequencing data. However, a variety of secondary metabolic activities in</div><div>plants (e.g. alkaloids, terpenoids, flavonoids, phenolic acids, and saponin) altered</div><div>lately using CRISPR/Cas-editing through knocking out, knocking in, and point</div><div>mutations, modulation of gene expression, including targeted mutagenesis.</div>

Natural products such as plants, animals, microorganisms, marine organisms have been used by humans to alleviate and treat diseases since the prehistoric ages which could be tracked back in 60,000 years. Traditional medicines have been practiced everywhere in the world; however, the most prominent ones are traditional Chinese medicine, Ayurveda in India, Kampo in Japan, Unani in Greek/Arabic, etc. A new study has revealed that 80% compounds of the current pharmaceutical compounds are one way, or another related to the natural sources. Lavenders, the genus Lavandula and a family of Lamiaceae, is a woody shrub, which are grown around the globe in diverse agro-ecologies mostly known for its essential oil composed of 30 – 40 aromatic compounds. Lavender essential oils (EOs) have long been natural remedies for various ailments. They possess potent calming and sedative effects, making them popular in aroma-therapeutic practices, as well as in cosmetic and food industries. Lavender EO quality depends on the composition of linalool, linalool acetate and camphor. Linalool and linalool acetate being favored in the cosmetic industries are termed true lavender oil compounds, and camphor, 1,8-cineole are being used mostly in the ointments and balms. Recent genomic and proteomic studies revealed all the structural and regulatory information related to lavender EO biosynthesis, also evident the relationship of lavender aromatic compounds in the benefit of human health. Information of secondary metabolites in lavenders or any medicinal plants will be important to formulate the natural health products based on the requirement.

A infecção pela bactéria Helicobacter pylori é considerada um problema de saúde pública, com intrínseca relação saúde e ambiente, a infecção bacteriana crônica mais comum no mundo, com alta prevalência em países em desenvolvimento. O uso de produtos naturais voltados a inovação medicamentosa, aumenta o interesse por novos princípios ativos a base de produtos naturais, contudo, a atividade antibacteriana forte ainda é controversa quanto a concentração inibitória mínima desses produtos, principalmente no que tage à H. pylori. Este trabalho realizou uma revisão sistemática dos produtos naturais com atividades anti-Helicobacter pylori disponíveis na literatura tendo como parâmetro inicial a revisão de plantas medicinais anti-H. pylori analisadas por Wang (2014) e como critério de classificação a concentração inibitória mínima. A pesquisa foi desenvolvida por meio da busca de artigos nas bases de dados online BVS, BDENF, LILACS, MEDLINE, PUBMED, Scielo, Bireme e ScienceDirect., os descritores utilizados foram: Helicobacter pylori, anti-Helicobacter pylori, produtos naturais, atividade antibacteriana, própolis e mel, traduzidos para o inglês. A busca resultou no total de 138 artigos, dos quais 59 artigos são da revisão de Wang (2014) e outros 79 foram encontrados nas bases de dados, que proporcionou um acréscimo de 57 artigos de plantas medicinas, 12 artigos de produtos distintos de plantas medicinais (mel, própolis, iogurte e cogumelo) e 10 artigos de estudos clínicos e in vivo. Foram encontrados 162 produtos naturais distintos, a maioria deles plantas medicinais, resultando na avaliação de 128 produtos naturais anti-Helicobacter pylori. Segundo a classificação de Wang somente 16 produtos apresentam atividade forte, e a maioria deles são frações. Com atividade forte-moderada mostra 45 produtos; com atividades moderada-fraca e fraca mostram 37 e 30 produtos, respectivamente. A nova classificação de produtos naturais com atividade anti-H. pylori proposta nessa pesquisa apresenta 5 classes de acordo com a sua concentração inibitória mínima: produtos com atividade forte, boa, moderada, fraca e sem atividade. Pela nova classificação proposta, apresentamos 43 produtos naturais com atividade forte, com 19 frações e 24 extratos; 40 produtos com atividade boa; 18 com atividades moderada e 15 produtos com fraca; na classificação sem atividade quatro produtos. A revisão ampliou os produtos naturais anti- Helicobacter pylori com novas plantas medicinais, produtos de origem animal e estudos clínicos e pré-clínicos. A nova classificação permitiu a inclusão de outros extratos vegetais, produtos de origem animal e fungos com atividade anti-Helicobacter pylori, e ampliou a faixa de produtos considerados com forte atividade.

Handbook of medicinal plants , Handbook of medicinal plants , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی